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Cigarette smoke effects on cells crucial for wound healing

Institution: University of California, Riverside
Investigator(s): Manuela Martins-Green, Ph.D.
Award Cycle: 2001 (Cycle 10) Grant #: 10IT-0170 Award: $74,500
Subject Area: General Biomedical Science
Award Type: Inno Dev & Exp Awards (IDEAS)
Abstracts

Initial Award Abstract
Tobacco smoking is one of the leading avoidable causes of death in the world. With time, it leads to cancer, hardening of the arteries, and to lung and kidney disease. Moreover, it also severely affects how active and passive smokers heal from injury. Wounds of smokers do not close well, potentially remaining as open sores which, with time, can become sites for local infection, spread systemically in the body, and become life-threatening. Moreover, problematic healing caused by smoke occurs in people of all ages (for example, in children living in the homes of smokers), not only in older individuals as is the case for most smoke-induced ailments. The problem of open sores is not only life-threatening but it also bears heavily on health care costs as people with open wounds frequently need to be hospitalized.

The goal of this application is to determine how passive and active smoking affect the process of wound closure. During wound healing, a variety of processes triggered by the formation of the clot lead to invasion of the wounded tissue by white blood cells that then mount a defensive reaction against microorganisms and produce molecules that stimulate fibroblasts, the “worker cells” of the wound. These cells divide to fill the wound, produce extracellular molecules that initially hold the wound together and provide pathways for incoming blood vessels (which oxygenate and nourish the wounded tissue), and contract the wound to help in its final closure.

Much is known about fibroblast function in wounds and about the process of healing itself, but not much is known about how tobacco smoke affects healing -- in particular how it affects wound closure. I propose that chemicals in cigarette smoke interfere with normal fibroblast function and thereby contribute to the difficulty in healing observed in the closure of wounds and the survival of skin grafts in both active and passive smokers. To address this problem, I will culture primary human skin fibroblasts under conditions that resemble the microenvironment in the human body and will treat them with both active and passive smoke to determine how the components of both types of smoke affect the functions of these cells. With the results of this work in hand, we will be able to progress to experiments that identify the components in the smoke responsible for the adverse affects, with the possibility of removing them from cigarettes or altering them in ways that they are no longer harmful. If that is not possible, this work will lead to understanding of the mechanisms by which these components affect healing and thereby to development of ways that can reverse the adverse smoke effects on wounds. Furthermore, these studies will lend themselves to preparation of educational materials that can be provided to teenagers and young adults to raise their awareness of the impact smoking can have on their health, and that of their children, today (not only when they are old).
Publications

Differential effects of active and passive cigarette smoke on febroblasts, cells that are critical for proper healing.
Periodical: Molecular Biology of the Cell Index Medicus:
Authors: Wong LS, and Martins-Green M ABS
Yr: 2001 Vol: 12 Nbr: Abs: Pg: 1213

Effects of Second-Hand smoke on structure and function of fibroblasts, cells that are critical for tissue repair and remodeling.
Periodical: BMC Cell Biology Index Medicus:
Authors: Wong LS, Green HM, Feugate JE, Yadav M, Nothnagel J, Martins-Green M ART
Yr: 2004 Vol: 5 Nbr: 13 Abs: Pg:

First Hand cigarette smoke alters fibroblast migration and survival: Implications for impaired healing.
Periodical: Wound Repair and Regeneration Index Medicus:
Authors: Wong LS, Martins-Green M ART
Yr: 2004 Vol: 12 Nbr: 4 Abs: Pg: 471-484

Effects of first-hand cigarette smoke on structure and function of fibroblasts.
Periodical: Molecular Biology of the Cell Index Medicus:
Authors: Wong L, Martins-Green M ABS
Yr: 2002 Vol: 13 Nbr: Abs: Pg: 727

Effects of second-hand smoke that can lead to impaired healing and fibrosis.
Periodical: Molecular Biology of the Cell Index Medicus:
Authors: Wong LS, Martins-Green M ABS
Yr: 2003 Vol: 14 Nbr: Abs: Pg: 355